The objective of this study is to determine the nucleotide sequence of the DNA replication region of bacteriophage T4. The results of this analysis will provide information about two aspects of bacteriophage DNA replication, namely, the primary structure of the major proteins of the T4 replication complex and the control of replication gene expression. The DNA replication region contains the genes coding for 4 of the 7 proteins required for T4 DNA replication (T4 DNA polymerase (43p) and the DNA polymerase proteins from the DNA sequence will provide a basis for interpreting both the x-ray diffration data on the crystallized proteins and the structure/function studies that will be carried out on the replicatiuon complex. Taken togehter these results will contribute to a detailed molecular model of DNA replication. The replication region of T4 also contains the reg A gene, which codes for aprotein that appears to act as atranslational repressor. The reg A protein controls the lvel of expression of several T4 proteins including some involved in DNA replication (44p, 62p and 45p) and the rIIB protein. In addition, there is evidence that the reg A proten controls the level of its own syntehsis. Nucleotide sequence analysis of the regulatory regions of the five genes contained in te replication region will reveal whether or not a specific reg A protein recognition sequence on the mRNAS can be identified. In addition, the DNA sequence will allow identification of the promoters and of the direction of transcription of the replication cistrons. These results should help to explain the temporal expression of T4 genes. Restriction fragments of the replication region of the T4 genome, comprising approximately 6.5 Kb, have already been clones in fragments into phage and plasmid vectors. These cloned fragments will be subcloned into M13 phage, which will facilitate DNA sequence analysis by the Sanger dideoxy method. The results of these studies should make significant contributions to our understanding of gene expression and DNA replication. Both processes play crucial roles in cell growth and viability and hence are of fundamental interest to medical research.